This proposal describes on-going research programs in biochemistry, molecular biology and immunology currently funded by NIH, which would substantially benefit from the capabilities of high sensitivity electrospray ultigenerational mass spectrometry. This proposal requests funds to purchase a liquid chromatograph Electrospray ion trap mass spectrometer and data system capable of the analysis of Copolymers up to molecule weights of 100,000 on sample amounts of 1 pmol or less. The instrument also has the capability of performing ultigenerational mass spectrometric analyses for unequivocal determination of molecular structure. The primary users are five faculty members in the University of Texas-Houston Medical School and on faculty member of the University of Texas M. D. Anderson Cancer Center who will utilize the spectrometer for both methodology development and specific applications in biomedical research. The principal investigator, R.M Caprioli, would utilize the instrument to continue development of microdialysis/microelectrospray mass spectrometric methods for in Vitro brain enzyme assays of neuropeptide proteases as well as the time-dependent production and quantitation of the proteolytic and other metabolic products of the tachykinin neuropeptides an opioid- related peptides in different brain structures. Co-investigators are Thomas Burke who will study the kinetics and differential processing of opioid peptide fragment precursors; Henry Strobel who will investigate the role of cytochromes P450 in the brain metabolism of haloperidol; George Weinstock who will study Jack Waymire who will investigate the stoichiometry of the phosphorylation of tyrosine hydroxylase in catecholaminergic cells; and Constantin loannides who will determine the identity of cytotoxic T cell peptides. The instrument would be housed in the Analytical Chemistry Center, a research resource which is supported by the Medical School and serves all of the faculty in the Health Science Center. The LC/MS" system would provide an important complement to the existing mass spectrometric instrumentation located in the Center.